Dettling, Steffen and Stamova, Slava and Warta, Rolf and Schnoelzer, Martina and Rapp, Carmen and Rathinasamy, Anchana and Reuss, David and Pocha, Kolja and Roesch, Saskia and Jungk, Christine and Warnken, Uwe and Eckstein, Volker and Grabe, Niels and Schramm, Christoph and Weigand, Markus A. and von Deimling, Andreas and Unterberg, Andreas and Beckhove, Philipp and Herold-Mende, Christel (2018) Identification of CRKII, CFL1, CNTN1, NME2, and TKT as Novel and Frequent T-Cell Targets in Human IDH-Mutant Glioma. CLINICAL CANCER RESEARCH, 24 (12). pp. 2951-2962. ISSN 1078-0432, 1557-3265
Full text not available from this repository. (Request a copy)Abstract
Purpose:Successful immunotherapies for IDH(mut )gliomas require better knowledge of T-cell target antigens. Here, we elucidated their antigen repertoire recognized by spontaneous T-cell responses using an unbiased proteomic approach. Experimental Design:Protein fractionations of tissue lysates from IDH(mut )gliomas (n = 4) were performed. Fractions were tested by IFN gamma ELISpot assay for recognition through patients' T cells. Proteins of immunogenic fractions were identified by mass spectrometry and validated byin silico-predicted synthetic long peptides in patients of origin, additional IDH(mut)glioma patients (n = 16), and healthy donors (n = 13). mRNA and protein expression of immunogenic antigens was analyzed in tumor tissues and IDH(mut)glioma stem-like cells (GSC). HLA-A*02-restricted T-cell epitopes were functionally determined by short peptides and numbers of antigen-specific T cells by HLA-peptide tetramer analysis. Results:A total of 2,897 proteins were identified in immunogenic tumor fractions. Based on a thorough filter process, 79 proteins were selected as potential T-cell antigens. Twenty-six of these were recognized by the patients' T cells, and five of them (CRKII, CFL1, CNTN1, NME2, and TKT) in up to 56% unrelated IDH(mut)glioma patients. Most immunogenic tumor-associated antigens (TAA) were expressed in IDH(mut)gliomas and GSCs, while being almost absent in normal brain tissues. Finally, we identified HLA-A*02-restricted epitopes for CRKII, NME2, and TKT that were recognized by up to 2.82% of antigen-specific peripheral cytotoxic T cells in IDH(mut)glioma patients. Conclusions:By analyzing the repertoire of T-cell target antigens in IDHmut glioma patients, we identified five novel immunogenic TAAs and confirmed their expression on IDH(mut )tumors and GSCs. (C)2018 AACR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ADAPTER PROTEIN CRK; CANCER; EXPRESSION; IMMUNOTHERAPY; ANTIGENS; CLASSIFICATION; ACTIVATION; STANDARD; VACCINES; THERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Mar 2020 13:29 |
| Last Modified: | 04 Mar 2020 13:29 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14393 |
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